Protein-tyrosine kinase receptors are important mediators of developmental signals in multicellular animals. The goal of the project in this application is to understand how receptor protein-tyrosine kinases are used in developmental processes in the simple animal Hydra. The attraction of Hydra as a system for these studies lies in the extreme simplicity of its structural organization and development. The initial approach to be taken will involve completing the molecular characterization of a gene from Hydra which is a member of a developmentally important class of receptor protein-tyrosine kinases in vertebrates. The cloned gene for this receptor will provide reagents for determining what cells in the polyp produce the receptor. With methods which we have developed for introduction of cloned genes and synthetic oligonucleotides into Hydro, it will be possible to carry out gain of function and loss of function experiments to determine what developmental processes depend on the receptor whose gene we have isolated. By expression studies it may be found that the receptor is expressed in the stem cells or committed precursors of a particular developmental lineage. If so, we can use antibodies against the receptor to isolate the cells which express it. These isolated cells can be introduced into stem cell- depleted Hydra polyps to determine their developmental fates. Such information will help in understanding how input via this receptor directs the development of cells. Because receptor protein-tyrosine kinases have been so well conserved during animal evolution, determining their roles in Hydra development should provide insight into how these proteins function in development in more complex animals. The well- documented involvement of receptor protein-tyrosine kinases in cell growth and differentiation and their ability to be converted to oncogenic forms indicate that an understanding of the roles these proteins play will have implications for understanding, diagnosing, and treating human diseases ranging from cancer to birth defects.
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